Since the isolation of Helicobacter pylori (hereinafter also referred to as HP) in 1983 [Lancet, 1, 1273 (1983)], its association with gastritis and digestive ulcer has drawn attention. This is because HP is found at high positivity rates in chronic gastritis or gastric ulcer [American Journal of Gastroenterology, 82, 2283 (1987)], despite the fact that it is normally not found in the mucosa of healthy humans [APMIS, 96, 84 (1988)].
On the other hand, the development of H.sub.2 blockers and proton pump inhibitors (hereinafter also referred to as PPI) has resulted in markedly improved healing rates for gastric/duodenal ulcer. However, there are some contractile cases in which no improvement occurs despite the appropriate treatment using these drugs, posing major problems. According to a report of such cases of contractile gastric ulcer [Japanese Journal of Gastroenterology, 89, 571 (1992)], the HP positivity rate is extremely high, with a reduction in the amount of gastromucosal mucus attributable to the ammonia produced by HP. Also, there are some reports of sustained infection with HP which delays ulcer healing or which is involved in ulcer recurrence [Lancet, 335, 1233 (1990); New England Journal of Medicine, 328, 308 (1993)]. Judging from these many clinical findings, HP elimination is believed to be useful in early healing of ulcer or prevention of its recurrence.
For the reasons described above, various anti-HP drugs have been administered to patients with gastric/duodenal ulcer. Although some PPIs possessing anti-HP activity have been developed, they remain unsatisfactory as to healing effect when used alone because their antibacterial action against HP is not always sufficient. Also, concomitant therapy has been performed with fair therapeutic results in which antiulcer agents such as H.sub.2 blockers and PPI are used in combination with antibacterial substances [Medical Journal of Australia, 151, 431 (1988); George LL et al., Medical Journal of Australia, 153, 145 (1990); Peterson WL et al., New England Journal of Medicine, 324, 1043 (1991); New England Journal of Medicine, 328, 308(1993)].
Antibacterial substances such as amoxicillin (hereinafter also referred to as AMOX), metronidazole (hereinafter also referred to as MZ), bismuth subacetate and tetracycline, have been used against HP singly or in combination; however, their administration often causes side effects such as diarrhea, nausea and retching because of the considerable doses (e.g., 750 mg of AMOX or 500 mg of MZ administered three times a day). Also, a pharmaceutical composition containing an anti-HP antibiotic (e.g., AMOX) and pantoprazol (WO 92/03135), and an administration comprising AMOX and omeprazole in combination (Scandinavian Journal of Gastroetherology, 24, 49 (1989) are reported, but their antiulcer action is unsatisfactory and their administration causes side effects as mentioned above.
Meantime, there have been developed gastrointestinal mucosa-adherent matrices to allow the preparation to adhere to the gastrointestinal mucosa to extend its retention in the gastrointestinal tract and hence improve the bioavailability of active ingredients. Although antiulcer agents, antigastritis agents etc. have been mentioned as active ingredients appropriate for use in the above-described preparation (EP-A-514008), none have been applied to formulation for concomitant therapy wherein at least one of them is prepared as a gastrointestinal mucosa-adherent solid preparation.